Optimizing Subcutaneous FEntanyl titRation: RApid Achievement of Adequate Exposure When Treating Cancer-Related paIn. (FERRARI)

The primary objective is to evaluate the effect of loading boluses when dose incresaing treatment with SC fentanyl in patients with cancer. The primary endpoint of this study is to prove the non-inferiority of fentanyl plasma concentrations 12 hours after dose augmentation compared to 48 hours after dose augmentation within each patient.

Patients will be treated with additional loading boluses and plasma-PK samples will be obtained.

Study Overview

• Status: Recruiting
• Conditions: Cancer Pain
• Intervention / Treatment: Drug: Fentanyl

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bram C Agema; Phone Number: +31107040704; Email: b.agema@erasmusmc.nl

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Recruiting
      • Erasmus Medical Center
      • Contact: Bram C Agema; Phone Number: +31107040704; Email: b.agema@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years;
• Able to understand the written information and able to give informed consent.
• Current or planned treatment with SC fentanyl for cancer-related pain

Exclusion Criteria:

• Pregnancy or/ and breastfeeding
• Other ways of using fentanyl (sublingual, nasal spray and oromucosal)
• Liver function CPS B or C
• The use of strong CYP3A4 inhibitors of inducers [9]
• Presence of somnolence, respiratory depression or CTCAE grade 2 adverse events.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm; Patients are given loading doses when dose-increasing fentanyl. The concentrations at 12 and 48 hours after dose increase will be compared	Drug: Fentanyl; Administration of subcutaneously administered fentanyl loading boluses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary endpoint of this study is to prove the non-inferiority in fentanyl plasma concentrations 12 hours after dose augmentation compared to 48 hours after dose augmentation within each patient using a bioequivalence approach	Using a paired t-test the geometric mean of the ratio of the two fentanyl plasma concentrations will be compared. The 90% confidence interval of the geomteric mean should fall within the range of 80 - 125%.	48 hours after dose increase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate the safety of the loading bolus strategy by assessing whether CTCAE grade III or higher occur as a consequence of the fentanyl loading boluses.	This will be performed as a descriptive analysis	up to 48 hours after dose increase
Describe the course of patient reported pain intensity in the 48 hours following the loading boluses.	This will be performed as a descriptive analysis	up to 48 hours after dose increase
Accurately assess the rate of fentanyl absorption after SC fentanyl administered as a bolus.	The pharmacokinetic data will be imputed into a population pharmacokinetic model that allows to simulate other situations and dosing regimens which will be used to further optimize dosing of subcutaneously administered fentanyl	up to 48 hours after dose increase

Collaborators and Investigators

• Sponsor: Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): December 2, 2025

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: July 5, 2024
• First Posted (Actual): July 12, 2024

Study Record Updates

• Last Update Posted (Actual): July 12, 2024
• Last Update Submitted That Met QC Criteria: July 5, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl
• Other Study ID Numbers: 2023-507355-30

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No